New Developments Influenza Virus Research: Finally Saying Goodbye to the Flu?

By Cai McCann


With the fall season ending, flu season swiftly closes in on us. Maybe you caught the flu, also known as the influenza virus, as quickly as the first wave, or maybe you’re gingerly holding friends and family at bay with the subsequent waves. And with each new fall season comes the roll out of a new flu vaccine.


With this in mind, biomedical spheres constantly search for innovative ways of targeting the influenza virus. As recent as mid-fall, researchers collaborating at Scripps Research, Washington University School of Medicine in St. Louis, and Icahn School of Medicine in New York discovered a new antibody capable of overcoming current issues for flu vaccines. In a series of stepwise, data-intensive studies, Daniel Stadlbauer, Xueyong Zhu, and others extracted monoclonal Ab (mAbs) from a human donor naturally infected with a specific strain of virus, a subtype called H3N2. Upon immunologically narrowing down three different possible candidate mAbs, they then cloned and checked the proteins’ ability to interact with other proteins, i.e. how well they bind. With each step of investigating protein binding, ability to inhibit the virus, it became more and more clear how effective the mAbs could be.

Artwork by Corinne Atkinson

These mAbs bind directly to epitopes within an enzyme’s active site or via proximal steric hindrance. And this effect was recapitulated in vivo in mouse models. Even when infecting mice with lethal doses of a wide diversity of influenza viruses, including Influenza virus A groups 1 and 2 (human, avian, and swine), and Influenza virus B within 72 hours after infection, the mAbs held up. To this end, it appears these mAbs can protect against a plethora of different viruses, demonstrating both successful binding of the mAbs and preventing mortality in mice. By extension, these new mAbs hold therapeutic potential in current vaccine research.


The current status quo includes vaccines with antibodies that target the primary protein, or glycoprotein, responsible for virus infection, hemagglutinin (HA). This protein resides on the surface of the virus and helps it bind to specific human host cell proteins (Byrd-Leotis et al., 2017). Unfortunately, it is also very mutable and so vaccines are strain-specific.


As a major virus surface glycoprotein, neuraminidase potentially represents the new holy grail for influenza vaccines. The natural function of neuraminidase is to release incoming viruses from infected cells and allow viruses to escape “sticky” host cell defense systems (Shtyrya et al., 2009). By “hacking” the system and instead using neuraminidase as a general signal for mAb to seek and attach to, we can obtain a broader, more “universal” vaccine against the influenza virus. As a follow up, the researchers of this study tested multiple viruses with the mAbs and all displayed a similar effect: the mAbs neutralized the virus, inhibited neuraminidase function, and thus provided a broad protective effect for the host organism.


While seemingly inconsequent, influenza virus, can easily and does affect everyone in some way or another. Just last year (2017-2018), the CDC estimates that as many as 49,000,000 people in the United States have reported flu-like symptoms (CDC, 2019). While it can be a minor inconvenience, it can also mean stolen time from learning in a classroom or decreasing productivity in the workplace. Additionally, with those CDC estimates, roughly 79,000 of these cases resulted in death.

How do we define success for a new vaccine? Both the successful preliminary results and the broad applications hint that this vaccine becoming more widely available and commonly accessible across different financials means, thereby preventing more deaths and maybe fewer days away from the workplace. Compared to a past of historically deadly influenza widespread infections, like the 1918 Spanish influenza pandemic that infected about one-third of the planet’s population and killed between 20 and 50 million individuals, influenza prevention has come quite far--but whether this new discovery in vaccine development is the catchall for our influenza problems remains the question and may require further observation.


References:


Byrd-Leotis, L., Cummings, R. D., & Steinhauer, D. A. (2017). The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase. International Journal of Molecular Sciences, 18(7). https://doi.org/10.3390/ijms18071541


CDC. (2019, October 31). Disease Burden of Influenza | CDC. Retrieved November 13, 2019, from Influenza (Flu) website: https://www.cdc.gov/flu/about/burden/index.html


Shtyrya, Y. A., Mochalova, L. V., & Bovin, N. V. (2009). Influenza Virus Neuraminidase: Structure and Function. Acta Naturae, 1(2), 26–32.


Stadlbauer, D., Zhu, X., McMahon, M., Turner, J. S., Wohlbold, T. J., Schmitz, A. J., … Krammer, F. (2019). Broadly protective human antibodies that target the active site of influenza virus neuraminidase. Science, 366(6464), 499–504. https://doi.org/10.1126/science.aay0678

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